The present study was undertaken to detect the effect of dietary protein level and feeding regime on the immune response of tilapia (Oreochromis niloticus). Twelve earthen ponds were used to represent twelve nutritional treatments (three protein levels 20, 25 and 30%, two feeding levels 3 and 5% and two feeding frequencies 2 and 3 times per day) infactorial manner (3x2x2). The actual experimental period lasted from May 16th to November 4th , located in Fish Research Station belonging to National Institute of Oceanography and Fisheries. The results indicated that the highest total Serum Protein (TSP) values as non-specific immunity were observed when fish fed 20% protein at a rate of 3% twice daily. The highest TSP's values wer observed in serum of fish fed on either 25% or 30% protein regardles feeding regime. The TSP's values were high when fish fed on 30% irrespective of protein level and feeding frequency. Concerning the feeding frequency, the highest TSP’ s values were recorded for fish fed twice daily. The highest values of albumin and globulin were observed in fish fed on 30% protein at a rate of 3% twice daily. Concerning protein levelirrespective of feeding regime, the highest values of albumin and globulin were observed for fish fed on 30% protein. While, the highes values of albumin and globulin were recorded for fish fed on 30% irrespective of protein level and feeding frequency. The highest values of albumin and globulin also, were observed for fish fed twice dial regardless protein level and feeding level. The results indicated that the highest Hydrogen Peroxidation titer values as humoralimmune response parameter were recorded in serum of fish fed on 20% protein, 5% twice daily or 25% protein, 3% twice daily, or 30% protein, 5% three times per day. Regardless of feeding regime, th highest Hydrogen Peroxidation titer was observed in serum of fish fed on either 25% or 20% on protein, while the highest hemolysin titer was found in serum of fish fed on 25% protein.